Effects of magnesium ions on recombinant human furin: selective activation of hydrolytic activity upon substrates derived from virus envelope glycoprotein.

Biological Chemistry
Mario A IzidoroLuiz Juliano

Abstract

Here we report a detailed analysis of magnesium (Mg²+) ion effects on furin hydrolysis of fluorescent resonance energy transfer decapeptide substrates derived from canonical R-X-K/R-R furin cleavage motifs within certain viral envelope glycoproteins and eukaryotic proproteins. Using virus-derived sequences a selective activation of furin by Mg²+) ions was observed as a result of cooperativity between furin subsites. Furin hydrolysis of the peptides Abz-SRRHKR↓FAGV-Q-EDDnp (from measles virus fusion protein F₀ and Abz-RERRRKKR↓GLFG-Q-EDDnp (from Asian avian influenza A, H5N1) was activated between 60- and 80-fold by MgCl₂. It appears that virus envelope glycoprotein mutations have been selected to increase their susceptibility to furin within cells, a location where Mg²+ is present in adequate concentrations for activation. Both the pH profile of furin and its intrinsic fluorescence were modified by Mg²+ ions, which bind to furin with a K(d) value of 1.1 mM.

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Citations

Sep 22, 2011·PloS One·Marcelo Y IcimotoVitor Oliveira
Apr 25, 2013·Antiviral Research·Antonella PasquatoStefan Kunz
Jun 8, 2017·Frontiers in Microbiology·Lucas M StangherlinMaria C C da Silva

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